This proposal is designed to increase our knowledge and understanding of reproductive biology and medicine in the male. This is a multidisciplinary and collaborative effort among basic scientists and clinical investigators, who are committed to advancing our understanding of reproductive physiology and translate this knowledge into improving human health and well-being. The proposed aims comprise the three major branches of the reproductive axis- the hypothalamus, pituitary and testes. The proposed research embraces both basic and clinical investigations, which have direct relevance to understanding certain disorders of human reproduction, including idiopathic hypogonadotropic hypogonadism, androgen insensitivity syndrome, meiotic arrest, Sertoli cell only syndrome, and oligospermia or azoospermia. Our clinical project is focused on understanding the functional significance of the hormonal and genetic environment required for spermatogenesis in men. The basic science projects investigate the neuroendocrine control of gonadotropin secretion, the molecular basis of the blood-testes barrier, and the key signaling pathways that regulate the development and function of mature gametes. Each project involves collaboration with at least one other in the Center, and the molecular physiology is integrated with the clinical investigation. We believe this approach will offer the best opportunity to provide the scientific rationale for the development of improved therapies to treat certain disorders of reproduction and serve as the basis for the development of better options for hormonal contraception in men. We are committed to scientific excellence and communication across disciplines, ranging from molecular biology to physiology and medicine. Our proposal incorporates the talents of outstanding investigators, whose experience and knowledge represent a rich and broad perspective on reproductive biology and its relevance to human health. We have deliberately structured the Center to bring together the best and most accomplished reproductive biologists and physician-scientists at the University of Washington in a scientific collaboration. We look forward to our continued participation in the NIH Specialized Cooperative Centers Program in Reproductive Research (SCCPRR). We share its goal of fostering communication, innovation and research excellence, with the ultimate goal of improving human reproductive health through accelerated transfer of discoveries made at the bench into clinical practice. We are committed to the collaborative spirit of the SCCPRR and have established collaborations with investigators at SCCPRR Programs at several other institutions. We look forward to contributing to the outstanding clinical and basic research in this important national program.